Background: The use of antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy insertion has been encouraged following development of guidelines by a number of professional societies within the past few years. However, not all evidence supports routine prophylaxis, particularly in patients with 'benign' disease indications for percutaneous endoscopic gastrostomy insertion. Aim: To identify whether prophylactic antibiotic usage is beneficial in patients undergoing percutaneous endoscopic gastrostomy insertion without malignant disease. Methods: Adult patients without malignant disease who were referred for percutaneous endoscopic gastrostomy insertion at our unit were assessed for participation in this prospective, double- blind, randomized controlled study. Patients were randomized to receive either placebo or 2.2 g co- amoxiclav ( or 2 g cefotaxime if penicillin- allergic) at time of percutaneous endoscopic gastrostomy insertion. Clinical endpoints studies were percutaneous endoscopic gastrostomy site or systemic infection and death within 7 days of percutaneous endoscopic gastrostomy insertion. Results: Ninety- nine patients completed the study ( 51 antibiotics, 48 placebo). Outcomes in the antibiotic and placebo groups respectively were: percutaneous endoscopic gastrostomy site infection, 11% vs. 47% ( P < 0.01); systemic infection, 16% vs. 38% ( P < 0.05); and death, 8% vs. 15% ( P = 0.5). Conclusions: Antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy insertion reduces both percutaneous endoscopic gastrostomy site and systemic infections in patients without malignant disease.